Preparation of liquid dispersions

ABSTRACT

A process for mixing or dispersing liquids is provided that includes introducing liquids to be mixed or dispersed into a mixing device having a cylindrical support. The cylindrical support includes an inlet nozzle having a bore which is in fluid communication through a turbulence chamber with a bore of an outlet nozzle, wherein the bores of the nozzles are axially spaced apart relative to one another. The liquids are then allowed to enter the turbulence chamber through the bore of the inlet nozzle where the liquids are mixed or dispersed. The mixed or dispersed liquid is then recovered from the outlet nozzle. Various devices for mixing or dispersing liquids are also provided.

This is a divisional of U.S. application Ser. No. 09/455,135, filed Dec.6, 1999 now U.S. Pat. No. 6,530,684.

FIELD OF THE INVENTION

The present invention provides a process for mixing or dispersingliquids. In particular, a process for the production of a finely dividedliquid dispersion is provided, as well as mixing devices for carryingout the process.

BACKGROUND OF THE INVENTION

European Patent Publication EP 0776 997 A1 describes a method for theproduction of a finely divided dispersion of solids in which apre-dispersion is pumped through one or more slotted nozzles. Theparticle size of the dispersed phase lies in the region of 0.01 μm to 20μm. The diameter of the nozzle bore is 0.05 mm to 1 mm. The ratio ofbore length to bore diameter is 1:1 to 1:10. A preferred combinationincludes a device which has two nozzle bodies with the nozzles lyingopposite their outlet. Also described are devices in which the crudedispersion or pre-dispersion is pumped through two or more nozzleshaving an equal or decreasing bore diameter. The slotted nozzle suitablyconsists of a ceramic material, for example, zirconium oxide, or a metalcoated with ceramic.

International Patent Publication WO 97/17946 describes a method for theproduction of a liposome dispersion in which an aqueous pre-dispersionof one or more amphiphilic substances is pumped at 600 bar to 900 barthrough at least one homogenizing nozzle having a diameter of 0.1 mm to0.5 mm. The homogenizing nozzle has an inlet channel and an outletchannel and includes a hard ceramic plate, in which the bore issituated, pressed in a steel body. The inlet channel and the outletchannel are also incorporated in the steel body. When several nozzlesare used, they are arranged opposite to each other and have a parallelinflow. The pre-dispersion is pumped in the circuit through thehomogenizing nozzle until the average particle size of the liposomedispersion is between about 35 nm and about 80 nm.

SUMMARY OF THE INVENTION

The devices described above suffer from the drawback that intermixing isoften inefficient or incomplete. Moreover, such devices require highamounts of energy to achive viable levels of intermixing.

Accordingly, it would be desirable to provide a method for mixing ordispersing liquids which permits an improved intermixing with lowerenergy expenditure compared with the state of the art.

One embodiment of the invention is a process for mixing or dispersingliquids that includes introducing liquids to be mixed or dispersed intoa mixing device having a cylindrical support. The cylindrical supportincludes an inlet nozzle having a bore which is in fluid communicationthrough a turbulence chamber with a bore of an outlet nozzle, whereinthe bores of the nozzles are axially spaced apart relative to oneanother. The liquids then enter the turbulence chamber through the boreof the inlet nozzle where the liquids are subjected to turbulence, i.e.,are mixed or dispersed. The mixed or dispersed product is thereafterrecovered from the outlet nozzle.

Another embodiment of the present invention is a mixing device having acylindrical support. The cylindrical support includes an inlet nozzlehaving a bore which is in fluid communication through a turbulencechamber with a bore of an outlet nozzle, wherein the bores of thenozzles are axially spaced apart relative to one another.

Another embodiment of the invention is a scale up arrangement wherein aplurality of nozzles are disposed within the cylindrical support.

A further embodiment of the invention is a scale up arrangement thatincludes a first support disk, a turbulence chamber, and a secondsupport disk, which are positioned in sequence in a conduit. The firstsupport disk consists of a plurality of inlet nozzles having a borediameter of about 0.05 mm to about 1 mm. The second support diskcontains a plurality of outlet nozzles having a bore diameter of about0.05 mm to about 1 mm. The bores of the inlet nozzles are in fluidcommunication with the bores of the outlet nozzles through theturbulence chamber and the bores of the inlet nozzles and outlet nozzlesare axially spaced apart relative to one another.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a flow diagram for carrying out the process in accordancewith the invention.

FIG. 2 shows a cross section through a mixing device in accordance withthe invention having an inlet nozzle and an outlet nozzle.

FIG. 3 shows a perspective view of the mixing device in accordance withthe invention.

FIGS. 4(a-c) shows a scale up arrangement.

FIG. 5 shows another a scale up arrangement.

DETAILED DESCRIPTION OF THE INVENTION

The present invention solves the problem of the previously describeddevices by pumping the liquids to be mixed or to be dispersed attemperatures of about 20° C. to about 250° C., preferably of about 20°C. to about 200° C., and pressures of about 50 bar to about 2500 bar,preferably of about 100 bar to about 800 bar, through a mixing devicewhich consists of one or more inlet nozzles, one or more turbulencechambers and one or more outlet nozzles, with the inlet nozzle(s),turbulence chamber(s) and outlet nozzle(s) being pressed in sequence ina cylindrical support. The bores of the inlet nozzles are in fluidcommunication with the bores of the outlet nozzles through theturbulence chamber and the bores of the inlet and outlet nozzles areaxially spaced apart relative to one another.

The process of the invention is especially suitable for the productionof finely divided dispersions having average particle sizes of about 10nm to about 1000 nm, preferably of about 50 nm to about 400 nm.

For the production of liquid dispersions, a pre-emulsion is pumpedthrough the aforementioned mixing device (dispersing unit). Thepre-emulsion is at temperatures of about 20° C. to about 250° C.,preferably of about 20° C. to about 200° C., and pressures of about 50bar to about 2500 bar, preferably of about 100 bar to about 800 bar.

The residence time of the liquids to be mixed or to be dispersed in themixing device is about 10⁻⁶ sec to about 10⁻¹ sec.

As used herein, the term “pre-emulsion” denotes one of the followingsystems:

a) oil-in-water emulsion (O/W emulsion);

b) water-in-oil emulsion (W/O emulsion);

c) oil-in-water emulsion in which a lipophilic active substance isdissolved in the oil; and

d) water immiscible solvent-in-water emulsion in which a lipophilicactive substance is dissolved in this solvent.

An oil-in-water emulsion in which the viscosity of the dispersed phaseis about 0.01 mPas to about 10,000 mPas, preferably about 0.1 mPas toabout 2000 mPas, is preferred.

As used herein, the term “lipophilic active substance” includes vitaminsA, D, E and K, carotenoids, and food additives, such as PUFAs(polyunsaturated fatty acids) and tocotrienols.

In the production of the pre-emulsion, the liquid to be dispersed ispreferably stirred into an aqueous emulsifier solution, optionally whilewarming.

The processes for the production of finely divided liquid dispersionsset forth herein relate not only to processes used in the foodmanufacturing field in which food emulsifiers are used, but also ingeneral industrial dispersion processes in which correspondingindustrial emulsifiers are used. Processes which are used in the foodmanufacturing field are preferred.

In the present invention, suitable emulsifiers/stabilizers fordispersions which may be added to foods include, for example, ascorbylpalmitate, lecithins, polysorbates, sugar esters, fatty acid esters,citric acid esters, sorbitol stearates; as well as colloids, for examplegelatines and fish gelatines; carbohydrates, for example starches andstarch derivatives such as dextrin, pectin or gum arabic; milk proteinsand plant proteins. Mixtures of the aforementioned substances can alsobe used. Ascorbyl palmitate, fish gelatines or starch derivatives arepreferred, with ascorbyl palmitate being especially preferred.

Suitable industrial emulsifiers are, for example, lauryl ethylene oxide(LEO)-9 and (LEO)-10.

The process in accordance with the invention is especially suitable forthe production of liquid dispersions from oils, such as, for example,corn oil, palm oil, sunflower oil, and the like. The present process mayalso be used to produce liquid dispersions from lipophilic activesubstances, such as, for example, from vitamin A, D, E, and K, fromcarotenoids or from food additives such as PUFAs and tocotrienols.

In the present invention, suitable carotenoids include, for example,beta-carotene, beta-apo-4′-carotenal, beta-apo-8′-carotenal,beta-apo-12′-carotenal, beta-apo-8′-carotenoic acid, astaxanthin,canthaxanthin, zeaxanthin, cryptoxanthin, citranaxanthin, lutein,lycopene, torularodin aldehyde, torularodin ethyl ester,neurosporaxanthin ethyl ester, zetacarotene, dehydroplectania-xanthinand the like.

The aforementioned lipophilic active substances may be used directlyinsofar as they are oily substances. Solid active substances, forexample carotenoids, may also be used in dissolved form in oil or inwater-immiscible solvents.

Suitable water-immiscible solvents that may be used in the presentinvention include halogenated aliphatic hydrocarbons, such as forexample, methylene chloride, water-immiscible esters, such as carboxylicacid dimethyl ester (dimethyl carbonate), ethyl formate, methyl, ethylor isopropyl acetate; or water-immiscible ethers such as for example,methyl tert.butyl ether, and the like.

The process in accordance with the invention provides a very efficientmixing or dispersing process for liquids. The mixing or dispersingprocess in accordance with the invention is also suitable for performingchemical reactions having very short reaction times, for example on theorder of seconds or fractions of seconds.

The mixing device in accordance with the invention has, in contrast tothe known devices described above, an arrangement of the bores of theinlet and outlet nozzles which is axially spaced apart relative to oneanother. Thus, by the turbulence chamber being positioned between thenozzles, the short term stability of mixtures, especially ofdispersions, is increased. This results in a liquid dispersion that ishomogenized more strongly.

In FIG. 1, a supply container (1) is followed by a high pressure pump(2) which is optionally connected to a heat exchanger (3). The mixingdevice (4) is positioned thereafter.

FIG. 2 and FIG. 3 show a mixing device (4) consisting of an inlet nozzle(6) having a bore diameter of about 0.05 mm to about 1 mm, preferablyabout 0.05 mm to about 0.5 mm; a turbulence chamber (7) having adiameter of about 0.5 mm to about 10 mm, preferably about 1 mm to about10 mm, such as about 1 mm to about 5 mm; an outlet nozzle (8) having abore diameter of about 0.05 mm to about 1.5 mm, preferably about 0.05 mmto about 0.8 mm, with the inlet nozzle (6), the turbulence chamber (7)and the outlet nozzle (8) being pressed in sequence in a cylindricalsupport (5). The inlet nozzle is in fluid communication with the outletnozzle via the turbulence chamber. The bores of the nozzles are axiallyspaced apart relative to one another.

As used herein, the phrase “fluid communication” is intended to meanthat liquids to be mixed or dispersed enter the turbulence chamberthrough the bore of the inlet nozzle. Once in the turbulence chamber,the liquids are mixed and then exit the chamber via the bore of theoutlet nozzle.

In the present invention, the bores of the nozzles are said to beaxially spaced apart relative to one another. Thus, as FIG. 2 indicates,the bores of the inlet and outlet nozzles are positioned on oppositesides of the axis of the chamber.

The ratio of length to diameter of each nozzle bore amounts in the caseof the inlet nozzle or the outlet nozzle to about 1 to 10, preferablyabout 1 to 5.

The ratio of length to diameter of the turbulence chamber is about 0.5to about 50, preferably about 0.5 to about 20, such as about 0.5 toabout 10.

The diameter of the turbulence chamber must be greater than the diameterof the outlet nozzle.

The bore diameters of the inlet nozzle and the outlet nozzle may be thesame or different. However, an embodiment in which the bore diameter ofthe inlet nozzle is smaller than the bore diameter of the outlet nozzleis preferred. For example, the bore diameter of the inlet nozzle isabout 0.2 mm and the bore diameter of the outlet nozzle is about 0.25mm.

The nozzles are suitably manufactured from wear-resistant materials suchas e.g. sapphire, diamond, stainless steel, ceramic, silicon carbide,tungsten carbide, zirconium, and the like.

The bores of the nozzles may be round, rectangular, or elliptical. Abore which has a cone in the mouth is also suitable.

The cylindrical support (5) likewise consists of wear-resistantmaterials, suitably of stainless steel.

FIG. 4 shows one possibility for the scale up of the mixing device.

Section 4 a shows a plurality of nozzles in accordance with theinvention with nozzle inserts (11), which are secured to a support plate(10). In the present invention, the nozzle inserts may be secured to thesupport plate by any conventional means, such as for example, they maybe screwed into the support plate. The support plate is positioned in aconduit (9) (cylindrical support).

Cross section 4 b shows only one nozzle insert (11′). The nozzle insert(11′), the support plate (10) as well as the conduit (9) aremanufactured from wear-resistant materials, preferably stainless steel.

Section 4 c shows the screwable nozzle support (11″) which contains thenozzle (4 c) in accordance with the invention.

FIG. 5 shows another scale up arrangement. In this arrangement, themixing device consisting of a support disk (12), a turbulence chamber(13) and a support disk (14), which are positioned in sequence in atubular conduit (15), with the first support disk (12) containing aplurality of inlet nozzles (16) having a bore diameter of about 0.05 mmto about 1 mm, preferably about 0.05 mm to about 0.5 mm, and the secondsupport disk (14) containing a plurality of outlet nozzles (17) having abore diameter of about 0.05 mm to about 1 mm, preferably about 0.05 mmto about 0.8 mm. The bores of the inlet nozzles are in fluidcommunication with the bores of the outlet nozzles through theturbulence chamber and the bores of the inlet nozzles and outlet nozzlesare axially spaced apart relative to one another.

The number of nozzles determines the diameter of the turbulence chamber(13). The ratio of length to diameter of the turbulence chamber isdesigned such that the residence time of a liquid to be dispersed in thedispersing unit is about 10⁻⁶ sec to about 10⁻¹ sec.

As set forth in FIG. 1, for the production of a finely divided liquiddispersion, a pre-emulsion is first produced in the supply container (1)in a known manner and pumped through the dispersing unit (4) attemperatures of about 20° C. to about 250° C., preferably about 20° C.to about 200° C., and pressures of about 50 bar to about 2500 bar,preferably about 50 bar to about 800 bar, using a high pressure pump(2). Where required, the pre-emulsion may be heated for a brief periodin the heat exchanger (3). The residence time of the liquid to bedispersed in the dispersing unit (4) is about 10⁻⁶ sec to about 10⁻¹sec.

The following examples are provided to further illustrate the presentprocess. These examples are illustrative only and are not intended tolimit the scope of the invention in any way.

In the Examples, in addition to the food emulsifier ascorbyl palmitate,industrial emulsifiers lauryl ethylene oxide (LEO)-9 and (LEO)-10 werealso used. This is a so-called “more rapid” emulsifier which veryrapidly stabilizes newly formed phase boundaries.

EXAMPLE 1 Corn Oil and Lauryl Ethylene Oxide

The emulsion had the following composition:

87 wt. % deionized water, 10 wt. % corn oil, and 3 wt. % lauryl ethyleneoxide-9.

Deionized water was placed in a kettle and warmed to 40° C. Theemulsifier lauryl ethylene oxide (LEO)-9 was dissolved in the water.Subsequently, the corn oil was stirred in and comminuted with an ULTRATURRAX mixer at 1000 rpm. When the content of dispersed phase was 10 wt.%, the weight ratio of corn oil to lauryl ethylene oxide was 10:3. Thepre-emulsion was homogenized three times at a pressure of 600 bar usingthe dispersing unit set forth in FIG. 2 in accordance with theinvention. The geometric dimensions of the dispersing units used are setforth in Table 1. The particle sizes were determined in a known mannerby means of photon correlation spectroscopy.

EXAMPLE 2 Corn Oil and Ascorbyl Palmitate

Here, ascorbyl palmitate was used as the emulsifier. The quantitativecomposition of the emulsion corresponded to that in Example 1.

Deionized water was placed in a kettle and warmed to 40° C. Ascorbylpalmitate was dissolved in the water at pH values between seven andeight. The production of the pre-emulsion and the homogenization werecarried out according to Example 1.

EXAMPLE 3 dl-alpha-Tocopherol and Ascorbyl Palmitate

dl-alpha-Tocopherol and ascorbyl palmitate were combined in accordancewith Example 2.

EXAMPLE 4 dl-alpha-Tocopherol and Ascorbyl Palmitate

A pre-emulsion was produced in accordance with Example 2. The content ofthe dispersed phase was 30 wt. %. The weight ratio ofdl-alpha-tocopherol to ascorbyl palmitate was 10:1. The pre-emulsion washomogenized once at pressures of 100 bar, 200 bar, 300 bar, 400 bar and500 bar using the dispersing unit in accordance with the invention shownin FIG. 2.

EXAMPLE 5 dl-alpha-Tocopherol, Corn Oil with Ascorbyl Palmitate and FishGelatine

An emulsion containing 65 wt. % deionized water, 6 wt. % ascorbylpalmitate, 4 wt. % fish gelatine, 18 wt. % dl-alpha-tocopherol and 7 wt.% corn oil was produced in the manner described hereinafter.

The deionized water was placed in a kettle and warmed to 60° C. The fishgelatine was dissolved in the water. Then, the ascorbyl palmitate wasdissolved in the aforementioned solution at pH values between seven andeight. Subsequently, the dispersed phase including dl-alpha-tocopheroland corn oil was stirred in as described in Example 1. The pre-emulsionwas homogenized in accordance with Example 4.

Examples 6-10 are comparative Examples using a single-hole nozzle.

EXAMPLE 6 Corn Oil and Lauryl Ethylene Oxide

The pre-emulsion was produced in accordance with Example 1 andhomogenized three times at a pressure of 600 bar in a single-holenozzle. The single-hole nozzle had an acute angled inlet and outlet. Thegeometric dimensions of the single-hole nozzle are given in Table 1.

EXAMPLE 7 Corn Oil and Ascorbyl Palmitate

The pre-emulsion was produced in accordance with Example 2 andhomogenized in the manner described in Example 6.

EXAMPLE 8 dl-alpha-Tocopherol and Ascorbyl Palmitate

The pre-emulsion was produced in accordance with Example 3 andhomogenized in the manner described in Example 6.

EXAMPLE 9 dl-apha-Tocopherol and Ascorbyl Palmitate

The pre-emulsion was produced in accordance with Example 4 andhomogenized once in a single-hole nozzle as described in Example 6 atpressures of 100 bar, 200 bar, 300 bar, 400 bar and 500 bar. Theparticle size was determined in a known manner by means of laserdiffraction spectrometry and photon correlation spectroscopy.

EXAMPLE 10 dl-alpha-Tocopherol, Corn Oil with Ascorbyl Palmitate andFish Gelatine

The pre-emulsion was produced in accordance with Example 5 andhomogenized once in a single-hole nozzle as described in Example 6 atpressures of 100 bar, 200 bar, 300 bar, 400 bar and 500 bar.

TABLE 1 Geometric dimensions of the dispersing units used. Length Borediameter Bore diameter of the Bore diameter of the of the turbulence ofthe Nozzle inlet nozzle turbulence chamber outlet nozzle type [mm]chamber [mm] [mm] [mm] Nozzle I 0.2 2 1.5 0.25 Nozzle I 0.2 2 3 0.28long Nozzle II 0.2 2 1.5 0.2 Single- 0.2 — — — hole nozzle

The average particle sizes of the finely divided liquid dispersions ofExamples 1-6 are set forth in Tables 2 and 3.

TABLE 2 Average particle sizes in nm of experiments 1, 2, 3, 6, 7 and 8.Passage 1 Passage 2 Passage 3 Example Nozzle type Particle size Particlesize Particle size 1 Nozzle I 218 202 202 0.2/0.25 mm 219 215 200 1Nozzle II 230 214 212 0.2/0.2 mm 231 220 208 6 single-hole 307 256 247nozzle 298 250 248 0.2 mm 2 Nozzle I 275 250 238 0.2/0.25 mm 2 Nozzle II294 266 245 0.2/0.2 mm 7 single-hole 340 320 275 nozzle 0.2 mm 3 NozzleI 295 287 267 0.2/0.25 mm 3 Nozzle II 312 294 302 0.2/0.2 mm 8single-hole 442 416 403 nozzle 0.2 mm

From Table I it is evident that the homogenization using nozzles I andII in accordance with the invention produces a liquid dispersion with asmaller particle size compared with the homogenization using asingle-hole nozzle. When nozzles I and II are used, particle sizes up toa third smaller are produced compared with the single-hole nozzle.

The best homogenization takes place in nozzle I. Here, the particle sizewas reduced to 200 nm after a triple homogenization. The values fromExample 1 reveal that the reproducibility of the results is also good.

The average particle sizes of the finely divided liquid dispersionsobtained in Examples 4, 5, 9, and 10 are set forth in Table 3.

TABLE 3 Average particle sizes in nm of experiments 4, 5, 9 and 10. 100bar 200 bar 300 bar 400 bar 500 bar Particle Particle Particle ParticleParticle Nozzle size size size size size Ex. type [nm] [nm] [nm] [nm][nm] 4 Nozzle I 1800 1370 1400 1105 1080 0.2/0.25 nm 4 Nozzle I/ 1370740 745 660 600 long 0.2/0.28 mm 9 Single-hole 5200 3080 1520 1370 914nozzle 0.2 mm 5 Nozzle I 435 410 340 350 345 0.2/0.25 mm 5 Nozzle I/ 420410 360 325 290 long 0.2/0.28 mm 10 Single-hole 440 430 360 350 355nozzle 0.2 mm

From Table 3 it is evident that the homogenization using nozzle I andnozzle I/long produce liquid dispersions with a smaller particle sizethan the homogenization using a single-hole nozzle. The besthomogenization takes place using nozzle I/long.

The invention being thus described, it will be obvious that the same maybe varied in many ways. Such variations are not to be regarded as adeparture from the spirit and scope of the invention, and all suchmodifications are intended to be included within the scope of thefollowing claims.

We claim:
 1. A mixing device for mixing or dispersing liquids in thepresence of an emulsifier comprising a first support disk, a turbulencechamber, and a second support disk, which are positioned in sequence ina conduit, the first support disk containing a plurality of inletnozzles having a bore diameter of about 0.05 mm to about 1 mm, and thesecond support disk containing a plurality of outlet nozzles having abore diameter of about 0.05 mm to about 1 mm, wherein the bores of theinlet nozzles are in fluid communication with the bores of the outletnozzles through the turbulence chamber, with the bores of the inletnozzles and outlet nozzles being axially spaced apart relative to oneanother, and wherein the ratio of length to diameter of the turbulencechamber is designed such that the residence time in the mixing device ofa liquid to be mixed or dispersed is about 10⁻⁶ seconds to about 10⁻¹seconds.
 2. A mixing device according to claim 1 wherein the borediameters of the inlet nozzles are about 0.05 mm to about 0.5 mm and thebore diameters of the outlet nozzles are about 0.05 mm to about 0.8 mm.